From the Yeast cell wall to new strategies in the fight against Ciguatera
Résumé
I will attempt to explain my scientific journey, from studying the cell wall and stress response
mechanisms of yeasts, up to the development of innovative approaches to fight Ciguatera, a major
cause of food poisonings by seafood worldwide.
Yeasts are eukaryotic microorganisms traditionally used by man to make bread, beer and wine
and thus very well studied. Their cells are surrounded by a thick cell wall composed of glycans and
proteins organized in a complex multilayered architecture. Essential for the survival of yeasts and
fungi, this highly dynamic organelle gets constantly remodeled during the cell cycle to allow
morphogenetic events as well as upon environmental changes. It is a key player in cellular adhesion
and resistance to antifungal compounds. While studying the mechanisms of cell wall adaptations to
various stresses, I came across the different cellular signaling pathways involved notably MAP kinase
cascades and the Calcineurin pathway which are conserved with higher eukaryotes.
Ciguatoxins (CTXs) are lipid-soluble, highly neurotoxic, polyether compounds produced by
dinoflagellates from the genus Gambierdiscus spp.. mostly found in tropical and subtropical zones.
CTXs bind to Voltage Gated Sodium Channels at the surface of human sensory neurons where they
remain, causing Ciguatera Fish Poisoning or CFP. This severe disease is characterized by with a
variety of gastrointestinal, cardiovascular and neurological symptoms (paresthesia, ataxia, cold
allodynia), including persistent neurological effects. Despite the importance and prevalence of CFP,
there is so far no simple and quick way of detecting these toxins in contaminated samples. Currently,
only heavy and expensive laboratory methods are available to detect them: LC-MS/MS, receptorbinding assays by competition with labeled compounds, and neuroblastoma cell-based assays
performed on mammalian neurons. We have started to engineer biosensors based on the detection of
a transcriptional signal in the model yeast Saccharomyces cerevisiae, using the very good
conservation of its signaling pathways with higher eukaryotes.
Finally, I will also present a smaller project (NeuroSens) based on a different strategy, to study
and characterize the binding of Ciguatoxins on mammalian neuronal cells by Single Molecule Force
Spectroscopy using Atomic Force Microscopy.
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